JP2020519298A5 - - Google Patents

Claims (17)

(A) Disconnectable domain;
(B) First antigen binding domain,
A first CAR comprising a first transmembrane domain and a first intracellular T cell signaling domain; and (c) a second antigen-binding domain,
A second CAR containing a second transmembrane domain and a second intracellular T cell signaling domain;
A chimeric antigen receptor (CAR) amino acid construct containing
The first and second CARs are linked through a severable domain and
(I) the first antigen binding domain comprises a heavy chain variable region CDR sequences, as well as a light chain variable region CDR sequences of SEQ ID NO: 12, 14, and 16 of SEQ ID NO: 4, 6, and 8, and <br / > If the first CAR is cleaved from the construct, does the first antigen binding domain have antigen specificity for CD22 ; or
(Ii) The first antigen binding domain comprises the light chain variable region CDR sequences of SEQ ID NOs: 24, 26, and 28, and the heavy chain variable region CDR sequences of SEQ ID NOs: 32, 34, and 36, and
When the first CAR is cleaved from the construct, the first antigen binding domain has antigen specificity for CD19, the construct. First antigen binding domain, a heavy chain variable region CDR sequences of SEQ ID NO: 4, 6, and 8, and a light chain variable region CDR sequences of SEQ ID NO: 12, 14, and 16, according to claim 1 CAR construct. First antigen binding domain comprises an amino acid sequence of the heavy chain variable region CDR sequences of the light chain variable region CDR sequences, and SEQ ID NO: 32, 34, and 36 of SEQ ID NO: 24, 26, and 28, in claim 1 The CAR construct described. Second antigen binding domains, the light chain variable region CDR sequences of SEQ ID NO: 24, 26, and 28, and comprises a heavy chain variable region CDR sequences of SEQ ID NO: 32, 34, and 36, according to claim 2 CAR construct. The CAR construct according to any one of claims 1 to 4 , wherein the cleaveable domain is 2A or furin. The CAR construct according to any one of claims 1 to 4, wherein the cleavable domain is 2A and furin. The CAR construct according to any one of claims 1 to 6 , wherein the CAR construct includes exactly two CARs, which are the first and second CARs, respectively. CAR is, SEQ ID NO: 48, 49, 50 and 51, Moshiku comprises an amino acid sequence having the amino acid sequence, or any one of 90% or more sequence identity with SEQ ID NO: 63 to 70 of 52, in claim 1 CA R co-Nsutorakuto described. The CAR according to claim 1, wherein the CAR comprises the amino acid sequence of SEQ ID NO: 49. (A) Two or more separable domains;
(B) First antigen binding domain,
A first CAR comprising a first transmembrane domain and a first intracellular T cell signaling domain; and (c) a second antigen-binding domain,
A second CAR containing a second transmembrane domain and a second intracellular T cell signaling domain;
A chimeric antigen receptor (CAR) amino acid construct containing
A construct in which the first and second CARs are linked via two or more cleavable domains. The CAR construct of claim 10 , wherein there are exactly two severable domains. Comprising a nucleotide sequence encoding a CAR amino construct of any one of claims 1 to 11, a nucleic acid. An isolated host cell comprising a recombinant expression vector comprising the nucleic acid of claim 12. Any one of the CAR construct of claim 1 to 11, nucleic acid according to claim 12, a host fine胞又of claim 13 comprising a cell population of its, and a pharmaceutically acceptable carrier, a pharmaceutical composition .. In a mammal, a pharmaceutical composition for the treatment of cancer, CAR construct of any one of claims 1 to 11, nucleic acid according to claim 12, the host cell or its cell population of claim 13 , Or a pharmaceutical composition comprising the pharmaceutical composition of claim 14 as an active ingredient. The pharmaceutical composition according to claim 15, wherein the cancer is a hematological malignancy. A method for producing a chimeric antigen receptor (CAR) amino acid construct.
(A) First antigen binding domain,
A first CAR comprising a first transmembrane domain and a first intracellular T cell signaling domain; and (b) a second antigen-binding domain,
A second CAR containing a second transmembrane domain and a second intracellular T cell signaling domain
Two or more severable domains are designed between, and the first and second CARs are linked through the two or more severable domains; and the first CAR, two or more severable domains. A method comprising cloning a plasmid containing a domain and a second CAR from N-terminus to C-terminus.